Multimodal fusion of radio-pathology and proteogenomics identify integrated glioma subtypes with prognostic and therapeutic opportunities

Abstract Integrating multimodal data can uncover causal features hidden in single-modality analyses, offering a comprehensive understanding of disease complexity. This study introduces a multimodal fusion subtyping (MOFS) framework that integrates radiological, pathological, genomic, transcriptomic,...

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Main Authors: Zaoqu Liu, Yushuai Wu, Hui Xu, Minkai Wang, Siyuan Weng, Dongling Pei, Shuang Chen, WeiWei Wang, Jing Yan, Li Cui, Jingxian Duan, Yuanshen Zhao, Zilong Wang, Zeyu Ma, Ran Li, Wenchao Duan, Yuning Qiu, Dingyuan Su, Sen Li, Haoran Liu, Wenyuan Li, Caoyuan Ma, Miaomiao Yu, Yinhui Yu, Te Chen, Jing Fu, YingWei Zhen, Bin Yu, Yuchen Ji, Hairong Zheng, Dong Liang, Xianzhi Liu, Dongming Yan, Xinwei Han, Fubing Wang, Zhi-Cheng Li, Zhenyu Zhang
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-58675-9
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author Zaoqu Liu
Yushuai Wu
Hui Xu
Minkai Wang
Siyuan Weng
Dongling Pei
Shuang Chen
WeiWei Wang
Jing Yan
Li Cui
Jingxian Duan
Yuanshen Zhao
Zilong Wang
Zeyu Ma
Ran Li
Wenchao Duan
Yuning Qiu
Dingyuan Su
Sen Li
Haoran Liu
Wenyuan Li
Caoyuan Ma
Miaomiao Yu
Yinhui Yu
Te Chen
Jing Fu
YingWei Zhen
Bin Yu
Yuchen Ji
Hairong Zheng
Dong Liang
Xianzhi Liu
Dongming Yan
Xinwei Han
Fubing Wang
Zhi-Cheng Li
Zhenyu Zhang
author_facet Zaoqu Liu
Yushuai Wu
Hui Xu
Minkai Wang
Siyuan Weng
Dongling Pei
Shuang Chen
WeiWei Wang
Jing Yan
Li Cui
Jingxian Duan
Yuanshen Zhao
Zilong Wang
Zeyu Ma
Ran Li
Wenchao Duan
Yuning Qiu
Dingyuan Su
Sen Li
Haoran Liu
Wenyuan Li
Caoyuan Ma
Miaomiao Yu
Yinhui Yu
Te Chen
Jing Fu
YingWei Zhen
Bin Yu
Yuchen Ji
Hairong Zheng
Dong Liang
Xianzhi Liu
Dongming Yan
Xinwei Han
Fubing Wang
Zhi-Cheng Li
Zhenyu Zhang
author_sort Zaoqu Liu
collection DOAJ
description Abstract Integrating multimodal data can uncover causal features hidden in single-modality analyses, offering a comprehensive understanding of disease complexity. This study introduces a multimodal fusion subtyping (MOFS) framework that integrates radiological, pathological, genomic, transcriptomic, and proteomic data from 122 patients with IDH-wildtype adult glioma, identifying three subtypes: MOFS1 (proneural) with favorable prognosis, elevated neurodevelopmental activity, and abundant neurocyte infiltration; MOFS2 (proliferative) with the worst prognosis, superior proliferative activity, and genome instability; MOFS3 (TME-rich) with intermediate prognosis, abundant immune and stromal components, and sensitive to anti-PD-1 immunotherapy. STRAP emerges as a prognostic biomarker and potential therapeutic target for MOFS2, associated with its proliferative phenotype. Stromal infiltration in MOFS3 serves as a crucial prognostic indicator, allowing for further prognostic stratification. Additionally, we develop a deep neural network (DNN) classifier based on radiological features to further enhance the clinical translatability, providing a non-invasive tool for predicting MOFS subtypes. Overall, these findings highlight the potential of multimodal fusion in improving the classification, prognostic accuracy, and precision therapy of IDH-wildtype glioma, offering an avenue for personalized management.
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spelling doaj-art-9f68f9d0684443b49917ae30c2fcf63c2025-08-20T03:06:54ZengNature PortfolioNature Communications2041-17232025-04-0116111810.1038/s41467-025-58675-9Multimodal fusion of radio-pathology and proteogenomics identify integrated glioma subtypes with prognostic and therapeutic opportunitiesZaoqu Liu0Yushuai Wu1Hui Xu2Minkai Wang3Siyuan Weng4Dongling Pei5Shuang Chen6WeiWei Wang7Jing Yan8Li Cui9Jingxian Duan10Yuanshen Zhao11Zilong Wang12Zeyu Ma13Ran Li14Wenchao Duan15Yuning Qiu16Dingyuan Su17Sen Li18Haoran Liu19Wenyuan Li20Caoyuan Ma21Miaomiao Yu22Yinhui Yu23Te Chen24Jing Fu25YingWei Zhen26Bin Yu27Yuchen Ji28Hairong Zheng29Dong Liang30Xianzhi Liu31Dongming Yan32Xinwei Han33Fubing Wang34Zhi-Cheng Li35Zhenyu Zhang36Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou UniversityShanghai Academy of Artificial Intelligence for ScienceDepartment of Interventional Radiology, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Neurosurgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Interventional Radiology, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Neurosurgery, The First Affiliated Hospital of Zhengzhou UniversityCenter of Reproductive Medicine, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Pathology, The First Affiliated Hospital of Zhengzhou UniversityDepartment of MRI, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Pathology, The First Affiliated Hospital of Zhengzhou UniversityInstitute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of SciencesInstitute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of SciencesDepartment of Neurosurgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Neurosurgery, The First Affiliated Hospital of Zhengzhou UniversitySchool of Medicine, Hangzhou City UniversityDepartment of Neurosurgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Neurosurgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Neurosurgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Neurosurgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Neurosurgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Neurosurgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Neurosurgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Neurosurgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Neurosurgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Neurosurgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Neurosurgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Neurosurgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Neurosurgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Neurosurgery, The First Affiliated Hospital of Zhengzhou UniversityInstitute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of SciencesInstitute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of SciencesDepartment of Neurosurgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Neurosurgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Interventional Radiology, The First Affiliated Hospital of Zhengzhou UniversityCenter for Single-Cell Omics and Tumor Liquid Biopsy, Zhongnan Hospital of Wuhan UniversityInstitute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of SciencesDepartment of Neurosurgery, The First Affiliated Hospital of Zhengzhou UniversityAbstract Integrating multimodal data can uncover causal features hidden in single-modality analyses, offering a comprehensive understanding of disease complexity. This study introduces a multimodal fusion subtyping (MOFS) framework that integrates radiological, pathological, genomic, transcriptomic, and proteomic data from 122 patients with IDH-wildtype adult glioma, identifying three subtypes: MOFS1 (proneural) with favorable prognosis, elevated neurodevelopmental activity, and abundant neurocyte infiltration; MOFS2 (proliferative) with the worst prognosis, superior proliferative activity, and genome instability; MOFS3 (TME-rich) with intermediate prognosis, abundant immune and stromal components, and sensitive to anti-PD-1 immunotherapy. STRAP emerges as a prognostic biomarker and potential therapeutic target for MOFS2, associated with its proliferative phenotype. Stromal infiltration in MOFS3 serves as a crucial prognostic indicator, allowing for further prognostic stratification. Additionally, we develop a deep neural network (DNN) classifier based on radiological features to further enhance the clinical translatability, providing a non-invasive tool for predicting MOFS subtypes. Overall, these findings highlight the potential of multimodal fusion in improving the classification, prognostic accuracy, and precision therapy of IDH-wildtype glioma, offering an avenue for personalized management.https://doi.org/10.1038/s41467-025-58675-9
spellingShingle Zaoqu Liu
Yushuai Wu
Hui Xu
Minkai Wang
Siyuan Weng
Dongling Pei
Shuang Chen
WeiWei Wang
Jing Yan
Li Cui
Jingxian Duan
Yuanshen Zhao
Zilong Wang
Zeyu Ma
Ran Li
Wenchao Duan
Yuning Qiu
Dingyuan Su
Sen Li
Haoran Liu
Wenyuan Li
Caoyuan Ma
Miaomiao Yu
Yinhui Yu
Te Chen
Jing Fu
YingWei Zhen
Bin Yu
Yuchen Ji
Hairong Zheng
Dong Liang
Xianzhi Liu
Dongming Yan
Xinwei Han
Fubing Wang
Zhi-Cheng Li
Zhenyu Zhang
Multimodal fusion of radio-pathology and proteogenomics identify integrated glioma subtypes with prognostic and therapeutic opportunities
Nature Communications
title Multimodal fusion of radio-pathology and proteogenomics identify integrated glioma subtypes with prognostic and therapeutic opportunities
title_full Multimodal fusion of radio-pathology and proteogenomics identify integrated glioma subtypes with prognostic and therapeutic opportunities
title_fullStr Multimodal fusion of radio-pathology and proteogenomics identify integrated glioma subtypes with prognostic and therapeutic opportunities
title_full_unstemmed Multimodal fusion of radio-pathology and proteogenomics identify integrated glioma subtypes with prognostic and therapeutic opportunities
title_short Multimodal fusion of radio-pathology and proteogenomics identify integrated glioma subtypes with prognostic and therapeutic opportunities
title_sort multimodal fusion of radio pathology and proteogenomics identify integrated glioma subtypes with prognostic and therapeutic opportunities
url https://doi.org/10.1038/s41467-025-58675-9
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